Evidence map›Paper›PMID 24498910›Full record

ArticleTissue engineering. Part A2014

Micropatterned cell-cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues.

Cheri Y Li, Kelly R Stevens, Robert E Schwartz, Brian S Alejandro, Joanne H Huang, Sangeeta N Bhatia

Open access · greenAbstract read
In one paragraph

Article in Tissue engineering. Part A, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
11.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

  1. Pooled it
  2. A 3D In Vitro Model of the Human Hepatobiliary Junction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Organoid scaffold materials: research and application.Frontiers in bioengineering and biotechnology · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Introducing CELLBLOKSIn vitro models · 2022
    Article
  12. Review
  13. Article
  14. Towards organoid culture without Matrigel.Communications biology · 2021
    Review
  15. Article
  16. Article
  17. Article
  18. Microphysiological Systems: Design, Fabrication, and Applications.ACS biomaterials science & engineering · 2020
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Cheri Y Li1 Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Kelly R Stevens
Robert E Schwartz
Brian S Alejandro
Joanne H Huang
Sangeeta N Bhatia
Massachusetts Institute of Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Tissue Chips for Rare Disease: Adding Timothy Syndrome to the HeLIVaSkCa platformUH3EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2014 to 2016
$7.1M
Engineering Multicellular Tissue Structure, Function, and VascularizationR01EB008396 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI BHATIA, SANGEETA N., CHEN, CHRISTOPHER S · 2009 to 2018
$5.8M
Modeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6M
Integrated heart-liver-vascular systems for drug testing in human health and diseUH2EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2012 to 2013
$1.7M
Howard Hughes Medical InstituteNCI NIH HHS P30-CA14051NIBIB NIH HHS R01 EB008396NIBIB NIH HHS UH2 EB017103NIBIB NIH HHS UH3 EB017103NIDDK NIH HHS R01 DK85713
6 · The paper itself

Abstract

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell-cell interactions and cell-matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell-cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug-drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms.

Indexed as

3T3 CellsAcetaminophenAlbuminsAnimalsCell CommunicationCells, CulturedCells, ImmobilizedCollagenCytochrome P-450 Enzyme SystemDrug InteractionsFemaleHepatocytesHydrogel, Polyethylene Glycol DimethacrylateMiceMicrofluidicsRats, Inbred LewAcetaminophenAlbuminsCollagenCytochrome P-450 Enzyme SystemHydrogel, Polyethylene Glycol Dimethacrylate

Identifiers

PMID24498910
PMCPMC4137334
OpenAlexW1994258387

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.